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To describe the methodology and implications of the patient-identified most bothersome symptom (PI-MBS) measure used in the phase 3, multicenter, randomized, double-blind, placebo-controlled, and parallel-group PROMISE-2 trial and to evaluate the contribution of this measure to the assessment of the preventive migraine benefits of treatment.
Learn More >To evaluate the analgesic efficacy of a portable, disposable and home self-applied transcutaneous electrical nerve stimulation device during migraine attacks.
Learn More >Humans with loss-of-function mutations in the Na1.7 channel gene (SCN9A) show profound insensitivity to pain, whereas those with gain-of-function mutations can have inherited pain syndromes. Therefore, inhibition of the Na1.7 channel with a small molecule has been considered a promising approach for the treatment of various human pain conditions. To date, clinical studies conducted using selective Na1.7 inhibitors have not provided analgesic efficacy sufficient to warrant further investment. Clinical studies to date used multiples of in vitro IC values derived from electrophysiological studies to calculate anticipated human doses. To increase the chance of clinical success, we developed rhesus macaque models of action potential propagation, nociception, and olfaction, to measure Na1.7 target modulation in vivo. The potent and selective Na1.7 inhibitors SSCI-1 and SSCI-2 dose-dependently blocked C-fiber nociceptor conduction in microneurography studies and inhibited withdrawal responses to noxious heat in rhesus monkeys. Pharmacological Na1.7 inhibition also reduced odor-induced activation of the olfactory bulb (OB), measured by functional magnetic resonance imaging (fMRI) studies consistent with the anosmia reported in Na1.7 loss-of-function patients. These data demonstrate that it is possible to measure Na1.7 target modulation in rhesus macaques and determine the plasma concentration required to produce a predetermined level of inhibition. The calculated plasma concentration for preclinical efficacy could be used to guide human efficacious exposure estimates. Given the translatable nature of the assays used, it is anticipated that they can be also used in phase 1 clinical studies to measure target modulation and aid in the interpretation of phase 1 clinical data.
Learn More >(1) Background: In many surgical procedures, regional analgesia (RA) techniques are associated with improved postoperative analgesia compared to systemic pain treatment. As continuous RA requires time and experienced staff, it would be helpful to identify settings in which continuous RA has the largest benefit. (2) Methods: On the basis of 23,911 data sets from 179 German and Austrian hospitals, we analyzed the association of perioperative RA with patient-reported pain intensity, functional impairment of movement, nausea and opioid use for different surgeries. Regression analyses adjusted for age, sex and preoperative pain were performed for each surgery and the following groups: patients receiving continuous RA (surgery and ward; RA++), RA for surgery only (RA+-) and patients receiving no RA (RA–). (3) Results: Lower pain scores in the RA++ compared to the RA– group were observed in 13 out of 22 surgeries. There was no surgery where pain scores for RA++ were higher than for RA–. If maximal pain, function and side effects were combined, the largest benefit of continuous RA (RA++) was observed in laparoscopic colon and sigmoid surgery, ankle joint arthrodesis, revision (but not primary) surgery of hip replacement, open nephrectomy and shoulder surgery. The benefit of RA+- was lower than that of RA++. (4) Discussion: The additional benefit of RA for the mentioned surgeries is larger than in many other surgeries in clinical routine. The decision to use RA in a given surgery should be based on the expected pain intensity without RA and its additional benefits.
Learn More >To test whether contralateral sensory abnormalities in the clinically unaffected area of patients with unilateral neuropathic pain are due to the neuropathy or pain mechanisms.
Learn More >Acute pain is the main complication of sickle cell disease. Chronic and neuropathic pain may also be experienced but have not been formally described in Jamaican patients. A cross-sectional study was conducted to determine their prevalence and characteristics, and to determine the common pain locations and modalities of management.
Learn More >Postoperative pain has a major influence on older adults' rehabilitation. There is a lack of knowledge regarding how older adults return to daily living after discharge.
Learn More >: Much is known about the impact of pain in terms of medical costs and missed work. Less is known about its associations when individuals are present for work. This study examines "presenteeism" by analyzing the psychosocial costs of pain in the workplace, using the 2015 European Working Conditions Survey (EWCS). : We conducted cross-sectional analysis of 2384 individuals with chronic pain and 2263 individuals without pain (matched by age and sex) using data from the 2015 EWCS. We compared groups in terms of the following psychosocial factors: supervisor support, job responsibility, team cohesion, discrimination, threats/abuse, job competency, job reward, sexual harassment, stress, and job security. The groups were also compared in terms of days lost due to illness. : People with pain were 64% less likely to view their job as rewarding (odds ratio [OR] = 0.61; 95% confidence interval [CI], 0.57-0.65), 47% more likely to be subjected to threats/abuse in the workplace (OR = 0.68; 95% CI, 0.63-0.73), 30% more likely to report poor supervisor support (OR = 0.77; 95% CI, 0.73-0.82), and 28% more likely to perceive discrimination in the workplace (OR = 0.78; 95% CI, 0.71-0.85). People with pain missed approximately nine more days of work per year than respondents without pain. : Chronic pain was associated with lower vocational fulfillment and feelings of being ostracized in the workplace. These findings suggest that the presence of pain in the workplace goes well beyond lost productivity due to absenteeism.
Learn More >Hereditary sensory neuropathies (HSN) are a group of rare neurological disorders with heterogeneous clinical and genetic characteristics. Although at least 17 different genes have already been associated with HSN, the epidemiology of the disorder in Brazil is still unknown. Performing whole genome sequencing (WGS) in 23 unrelated Brazilian families diagnosed with HSN, we detected pathogenic variants in ATL3, SPTLC2, and SCN9A in 12 patients belonging to five unrelated families. Clinical features associated with heterozygous mutations in ATL3 (c.575A > G; p.(Tyr192Cys)) and SPTLC2 (c.529A > G; p.(Asn177Asp)) were sensory deficits, neuropathic pain, and recurrent ulcerations. Presenting as congenital insensitivity to pain, three unrelated probands carried biallelic loss-of-function mutations in SCN9A. The so far undescribed stop mutation c.2106G > A (p.(Trp702Ter)) and the likewise novel splicing variant c.3319-1G > A were found in compound-heterozygosity with, respectively, the known pathogenic variants c.2908G > T (p.Trp970Ter) and c.2690G > A (p.Glu897Ter). In total, we identified pathogenic mutations in 21.7% of our families, which suggests that most of the cases could be explained by yet to be discovered genes or unusual alleles. Our study represents the first mutational screen in a Brazilian HSN cohort, enabling additional insights for genotype-phenotype correlations, reducing misdiagnoses, and providing early treatment considerations.
Learn More >Patients with chronic pain who are tapering prescription opioids report a need for greater support for coping with symptoms of pain and withdrawal. Mobile health (mHealth) technologies (SMS text messaging- or app-based) have the potential to provide patients with educational, emotional, and motivational support for opioid tapering beyond what is offered by their health care provider. However, it is not known whether patients with chronic pain who are tapering opioids would be willing or able to engage with technology-based support.
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